Muscle metabolism is affected by many different processes such as physical activity and age. For example, muscle protein synthesis is increased by elevated level of physical exercise, such as in the case of athletes. Muscle protein synthesis is also known to be more important in children during growth than in adults. Indeed, during growth and until they are adults, children gain a large mass of muscle, predominantly of skeletal muscle rich in type I fibers, also called slow twitch fiber rich muscles. Muscle enrichment in type I fibers is favored by endurance exercise and thwarted by physical inactivity. Muscle enrichment in type I fibers is considered a favorable factor in the prevention of metabolic syndrome and related disorders.
Different products have been found that promote protein synthesis. However, skeletal muscle fibers are not all the same. Indeed, in comparison with fast twitch muscles, slow twitch muscles tend to have a low activity level of ATPase, a slower speed of contraction with a less developed glycolytic capacity. They have been demonstrated to have high concentrations of mitochondrial enzymes, thus they are fatigue resistant. Importantly, research has shown that protein synthesis is differently regulated depending on the muscle fiber type (Goodman et al., PLoS One; 7(5); 2012). Despite this very well-known fact, no product has been discovered yet that can increase muscle protein synthesis specifically in slow twitch fiber-rich muscles. Moreover, most of the existing products have proven adverse effects, and would probably not be safe for a child.
EP 2 583 566 for example discloses whey protein micelles, susceptible to enhance muscle mass and performance. However, while whey protein micelles represent an optimized form of protein supply, they do not promote protein synthesis on the long term and do not specifically improve protein synthesis of type I muscle fibers, nor muscle mass and performance in slow twitch fiber rich muscles. In addition, high doses of whey protein can cause some side effects such as increased bowel movements, nausea, thirst and may in the long term compromise kidney function.
WO 2001/056402 discloses alpha lipoic acid-based food supplement able to increase lean muscle mass and strength, yet this increase does not seem to occur specifically in slow twitch fiber-rich muscles. Moreover, alpha lipoic acid may induce skin rash in humans. Further, it is recommended that people with diabetes be particularly cautious when taking alpha lipoic acid, because it affects blood sugar regulation.
Some products intended for increasing muscle mass claim to have low to no side effects. For instance, FR 2 907 011 discloses that the use of citrulline increases protein synthesis in the muscle with no side effect. Yet, the administration of citrulline does not appear to enable an increase in protein synthesis specifically in type I muscle fibers.
Therefore, to date, no product has been shown to be able to support or enhance muscle protein synthesis specifically in slow twitch fiber-rich muscles, with low to no toxicity.
There is thus a need for improved compositions for enhancing muscle protein synthesis in a subject, which do not present adverse effects and target preferably skeletal muscles.
On the other hand, most muscle-wasting associated disorders, and in particular wasting which occurs with ageing, have currently no cure, and patients would obviously benefit from any medication capable of preventing or treating those disorders.
Hence, there is also a need for medicaments for the prevention or treatment of muscle-wasting associated disorders.